Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Genome-wide activity of unliganded Estrogen Receptor alpha in breast cancer cells [ChIP-Seq]

ABSTRACT: Estrogen Receptor ? (ER?) has central role in hormone-dependent breast cancer and its ligand-induced functions have been extensively characterized. However, evidence exists that ER? has functions which are independent of ligands. In the present work, we investigated the binding of ER? to chromatin in absence of ligands, and its function(s) on gene regulation. We demonstrated that in MCF7 breast cancer cells unliganded ER? binds to more than four thousands chromatin sites. Unexpectedly, although almost entirely comprised in the larger group of estrogen-induced binding sites, we found that unliganded-ER? binding is specifically linked to genes with developmental functions, as compared to estrogen-induced binding. Moreover, we found that siRNA-mediated downregulation of ER? in absence of estrogen is accompanied by changes in the expression levels of hundreds of coding and noncoding RNAs. Downregulated mRNAs showed enrichment in genes related to epithelial cell growth and development. Stable ER? downregulation using shRNA, which caused cell-growth arrest, was accompanied by increased H3K27me3 at ER? binding sites. Finally, we found that FOXA1 and AP2? binding to several sites is decreased upon ER? silencing, suggesting that unliganded ER? participates, together with other factors, to the maintenance of the luminal-specific cistrome in breast cancer cells. Examination of unligandend estrogen receptor alpha (apoER?) DNA interactions in control and ER? siRNA treated MCF7 cells.

ORGANISM(S): Homo sapiens

SUBMITTER: Giulio Ferrero

PROVIDER: E-GEOD-53531 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Estrogen receptors play critical roles in both the normal physiological, and disease states of numerous tissues, including breast and uterus. Estrogen receptor alpha (ER) can activate or repress the expression of target genes upon estrogen stimulation. In order to better understand the transcriptional network of ER in breast and uterus, we generated genome wide maps ofM-BM- ER binding sites (ERBS) and gene expression profiles in breast cancer cells (MCF7 and T47D) and uterine cancer cells (ECC1 and Ishikawa) through ChIP-Seq and microarray techniques. Surprisingly, we identified large scale differences in the numbers of ERBS between these cell lines when treated with E2 (17-M-NM-2 estradiol). Besides identification of common and unique ERBS between breast and uterine cancer cell types., our data also suggest that both cell types could recruit a large set of common co-operating transcription factors (Co-TFs) and a few unique Co-TFs as well. Besides the genes that are commonly regulatedM-BM- between the different cell lines, there are a number of genes that are differentially regulated in different cell types. Gene pathway analyses of E2 target genes suggest that ER regulates many biological pathways and processes in both tissue-type dependent and independent manners. Our results showed that cell lines derived from same tissue display a greater similarity for both profiles of ERBS and gene expression, and that the differential profiles of ER and preferential recruitment of some Co-TFs are the main determinants for the differential regulation of E2 signaling in breast and uterine cancer cells. In order to explore common and distinctive features of ERM-NM-1 (estrogen receptor alpha) binding profiles between breast and uterus, we generated eight ChIP-Seq libraries for the four cell lines (MCF7, T47D, ECC1 and Ishikawa) under two different treatments (E2, ethanol). In addition, we generated four control libraries for the four cell lines. For all treatment libraries, we generated about 7-12 million unique tags each. ER antibody catalog number is (Santa Cruz,sc-543).

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Genome-wide activity of unliganded Estrogen Receptor alpha in breast cancer cells [ChIP-Seq]

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